International journal of molecular sciences
January 5, 2024
Sofía Villalba, Bruno González, Stephanie Junge et al.
9 citations
Noribogaine, the primary metabolite of ibogaine, produces sexually dimorphic effects in mice, with some responses depending on the 5-HT2A receptor. A single 40 mg/kg dose reduced locomotion in male but not female wild-type mice. Gene expression of immediate early genes and glutamate receptors differed by sex and genotype. 5-HT2A receptor mRNA increased in the medial prefrontal cortex after noribogaine at 10 mg/kg in males and 40 mg/kg in females. Electrophysiology showed that 40 mg/kg reduced NMDA-mediated postsynaptic current density in layer V pyramidal neurons of the medial prefrontal cortex only in male wild-type mice, an effect absent in 5-HT2A receptor knockout males and all females. The genetic removal of the 5-HT2A receptor blunted noribogaine's effects on NMDA synaptic transmission.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
August 1, 2025
Sofía Villalba, Sofia Bosch, Lucia di Constanzo et al.
1 citation
Noribogaine, the primary metabolite of the atypical psychedelic ibogaine, alters thalamic calcium channel gene expression and current density in mice in a sex- and 5-HT2A receptor-dependent manner. A single injection of 10 mg/kg noribogaine increased CACNA1g (T-type) mRNA expression only in wild-type males and knockout females, indicating receptor- and sex-specific effects. The same dose increased CACNA1a (P/Q-type) expression in both sexes and decreased HCN2 expression in females of both genotypes but only in knockout males. Bath-applied noribogaine (50 μM) blocked T-type calcium current density only in knockout females, not in wild-type females or males. Baseline calcium current density was also higher in female ventrobasal neurons, further suggesting sex-dependent differences.
Pharmacology Biochemistry and Behavior
July 9, 2026
Sofía Villalba, Agustín Martínez Christensen, Lucia di Costanzo et al.
Psychedelics show promise as therapeutic interventions for depression, terminal illnesses, substance use disorder, neurodegenerative diseases, trauma, and obsessive-compulsive disorder. Research on psychedelics has advanced understanding of the neurobiological mechanisms behind the 'psychedelic state of consciousness' and both physiological and pathological thalamocortical functioning. Several psychiatric conditions—such as depression, schizophrenia, bipolar disorder, and autism—involve alterations in the thalamocortical system, so deeper understanding of thalamic function could significantly impact psychedelic research and biological psychiatry. This scoping review (using the PRISMA method) synthesizes preclinical and clinical evidence on effects of psychedelics (NMDA receptor antagonists, serotonin 2A receptor agonists, and mixed-pharmacology compounds like iboga alkaloids) on the thalamocortical system, suggesting its importance for clinical practice and understanding psychedelic neurobiology.